2009-至今 终身教授 拉荷亚(La Jolla)过敏与免疫研究所美国
1997-2009 助理教授、副教授 拉荷亚(La Jolla)过敏与免疫研究所美国
1993-1997 博士后研究员 拉荷亚(La Jol la)过敏与免疫研究所美国
1988-1993 博士 群马大学( Gunma University )日本
研究领域与方向 蛋白底物经过一些列酶反应过程与泛素结合而泛素化,蛋白一经泛素化将传递一种信号至蛋白降解系统使得被降解清除。及时清除有害或者过多的蛋白对维持细胞的正常功能极为重要,这种功能紊乱将导致各种疾病的发生如癌症、免疫学疾病等。
Cbl家族蛋白作为一种E3泛素连接酶接头蛋白能够将泛素转移到特定蛋白底物上,我们的研究结果发现Cbl家族成员Cbl-b蛋白分子对于机体T细胞的稳态极为重要,Cbl-b的缺失将会导致T细胞的过度活化以至于形成对自身组织和器官的免疫攻击,最终导致关节炎和糖尿病等的发生。
我们也对该家族其他成员进行研究,比如另外一个E3泛素连接酶ITCH ,我们发现其在Th2细胞的分化过程中起着极为重要的作用,后者能释放大量的过敏性介质。ITCH的缺失将会导致Th2的功能异常乃至发生过敏性哮喘。因此,我们的目的就是要深入研究泛素系统在机体免疫调节过程中的作用,以为我们今后设计针对一些免疫疾病如关节炎、糖尿病、哮喘等的干预治疗提供新思路。
学术荣誉与奖励
关键词T细胞免疫, 自身免疫病,泛素化蛋白对淋巴细胞功能调节及其在自身免疫病等异常免疫应答过程中的作用
代表性论文1. Neddylation pathway regulates T-cell function by targeting an adaptor protein Shc and a protein kinase Erk signaling.Proc Natl Acad Sci U S A. 2013
2. To go or not to go: the "itchy" effect on the destiny of hematopoietic stem cells. Cell Res. 2011
3. K33-linked polyubiquitination of T cell receptor-zeta regulates proteolysis-independent T cell signaling. Immunity. 2010
4. Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells. J Exp Med. 2010
5. Mechanisms of NKT cell anergy induction involve Cbl-b-promoted monoubiquitination of CARMA1. Proc Natl Acad Sci USA. 2009
6. The E3 ubiquitin ligase Itch regulates expression of transcription factor Foxp3 and airway inflammation by enhancing the function of transcription factor TIEG 1. Nat Immunol.2008
7. Negative Regulation of the E3 Ubiquitin Ligase Itch via Fyn-Mediated Tyrosine Phosphorylation. Mol Cell. 2006
8. Immunity by ubiquitylation: a reversible process of modification. Nat Rev Immunol. 2005
9. Ubiquitin ligases and the immune response. Annu Rev Immunol. 2004
10.Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch.Science. 2004
11.Itch E3 ligase-mediated regulation of TGF-Beta signaling by modulating Smad2 phosphorylation. Mol Cell. 2004
12.Essential Role of the E3 Ubiquitin Ligase Cbl-b in T Cell Anergy Induction. Immunity.2004
13.Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiation.Nat Immunol. 2002
14.The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase. Science. 1999
15.Proteolysis-independent regulation of phosphatidylinositol 3-kinase by Cbl-b-mediated ubiquitination in T cells. Nature Immunol. 2001
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